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Eosinophils improve cardiac function after myocardial infarction

Authors :: Dafeng Yang
Xian Zhang
Dazhu Li
Axel Cosmus Pyndt Diederichsen
Yunzhe Wang
Tianxiao Liu
Zhiyong Deng
Chongzhe Yang
Cong-Lin Liu
Lars Melholt Rasmussen
Jing Liu
Jing Wang
Peter Libby
Francis W. Luscinskas
Gail Newton
Wenqian Fang
Lijun Liu
Qin Huang
Guo-Ping Shi
Galina K. Sukhova
Junli Guo
Jes S. Lindholt
Jie Li
Source :: Liu, J, Yang, C, Liu, T, Deng, Z, Fang, W, Zhang, X, Li, J, Huang, Q, Liu, C, Wang, Y, Yang, D, Sukhova, G K, Lindholt, J S, Diederichsen, A, Rasmussen, L M, Li, D, Newton, G, Luscinskas, F W, Liu, L, Libby, P, Wang, J, Guo, J & Shi, G-P 2020, ' Eosinophils improve cardiac function after myocardial infarction ', Nature Communications, vol. 11, 6396 . https://doi.org/10.1038/s41467-020-19297-5, Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020), Nature Communications, Liu, J, Yang, C, Liu, T, Deng, Z, Fang, W, Zhang, X, Li, J, Huang, Q, Liu, C, Wang, Y, Yang, D, Sukhova, G K, Lindholt, J S, Diederichsen, A, Rasmussen, L M, Li, D, Newton, G, Luscinskas, F W, Liu, L, Libby, P, Wang, J, Guo, J & Shi, G P 2020, ' Eosinophils improve cardiac function after myocardial infarction ', Nature Communications, vol. 11, 6396 . https://doi.org/10.1038/s41467-020-19297-5
Publication Year :: 2020
Abstract: Clinical studies reveal changes in blood eosinophil counts and eosinophil cationic proteins that may serve as risk factors for human coronary heart diseases. Here we report an increase of blood or heart eosinophil counts in humans and mice after myocardial infarction (MI), mostly in the infarct region. Genetic or inducible depletion of eosinophils exacerbates cardiac dysfunction, cell death, and fibrosis post-MI, with concurrent acute increase of heart and chronic increase of splenic neutrophils and monocytes. Mechanistic studies reveal roles of eosinophil IL4 and cationic protein mEar1 in blocking H2O2- and hypoxia-induced mouse and human cardiomyocyte death, TGF-β-induced cardiac fibroblast Smad2/3 activation, and TNF-α-induced neutrophil adhesion on the heart endothelial cell monolayer. In vitro-cultured eosinophils from WT mice or recombinant mEar1 protein, but not eosinophils from IL4-deficient mice, effectively correct exacerbated cardiac dysfunctions in eosinophil-deficient ∆dblGATA mice. This study establishes a cardioprotective role of eosinophils in post-MI hearts.<br />Blood eosinophil (EOS) counts may serve as risk factors for human coronary heart diseases. Here the authors show that increased circulating and myocardial EOS after myocardial infarction play a cardioprotective role by reducing cardiomyocyte death, cardiac fibroblast activation and fibrosis, and endothelium activation-mediated inflammatory cell accumulation.